title: HIV-1 drug resistance prevalence, drug susceptibility and variant characterization in the Jacobi Medical Center paediatric cohort, Bronx, NY, USA.
abstract: OBJECTIVE
  With the advent of combined antiretroviral therapy (cART), perinatally HIV-infected children are surviving into adolescence and beyond. However, drug resistance mutations (DRMs) compromise viral control, affecting the long-term effectiveness of ART. The aims of this study were to detect and identify DRMs in a HIV-1 infected paediatric cohort.
  
  
  METHODS
  Paired plasma and dried blood spots (DBSs) specimens were obtained from HIV-1 perinatally infected patients attending the Jacobi Medical Center, New York, USA. Clinical, virological and immunological data for these patients were analysed. HIV-1 pol sequences were generated from samples to identify DRMs according to the International AIDS Society (IAS) 2011 list.
  
  
  RESULTS
  Forty-seven perinatally infected patients were selected, with a median age of 17.7 years, of whom 97.4% were carrying subtype B. They had a mean viral load of 3143 HIV-1 RNA copies/mL and a mean CD4 count of 486 cells/μL at the time of sampling. Nineteen patients (40.4%) had achieved undetectable viraemia (< 50 copies/mL) and 40.5% had a CD4 count of > 500 cells/μL. Most of the patients (97.9%) had received cART, including protease inhibitor (PI)-based regimens in 59.6% of cases. The DRM prevalence was 54.1, 27.6 and 27.0% for nucleoside reverse transcriptase inhibitors (NRTIs), PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Almost two-thirds (64.9%) of the patients harboured DRMs to at least one drug class and 5.4% were triple resistant. The mean nucleotide similarity between plasma and DBS sequences was 97.9%. Identical DRM profiles were present in 60% of plasma-DBS paired sequences. A total of 30 DRMs were detected in plasma and 26 in DBSs, with 23 present in both.
  
  
  CONCLUSIONS
  Although more perinatally HIV-1-infected children are reaching adulthood as a result of advances in cART, our study cohort presented a high prevalence of resistant viruses, especially viruses resistant to NRTIs. DBS specimens can be used for DRM detection.
authors.affiliation: HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Ramón y Cajal University Hospital-IRyCIS, Madrid, Spain; Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: de Mulder
authors.forename: V A
authors.initials: VA
authors.lastname: York
authors.forename: A A
authors.initials: AA
authors.lastname: Wiznia
authors.forename: H A
authors.initials: HA
authors.lastname: Michaud
authors.forename: D F
authors.initials: DF
authors.lastname: Nixon
authors.forename: A
authors.initials: A
authors.lastname: Holguin
authors.forename: M G
authors.initials: MG
authors.lastname: Rosenberg
mesh_terms: D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D002675:Child, Preschool; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010802:Phylogeny; D011480:Protease Inhibitors / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014481:United States; D019562:Viral Load; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054302:pol Gene Products, Human Immunodeficiency Virus
keywords: HIV; dried blood specimens; drug resistance; drug susceptibility; paediatric